JP4143807B2 - Dermal regeneration base material - Google Patents

Description

【００３６】
（３）圧縮特性試験
以下の条件で、圧縮特性試験を３回繰り返し、その平均値を算出した。結果を表２に示す。
使用機器:KES-FB3(KATO TECH.Ｃo.Ltd.)
Speed：50mm/mim
Zone：2ｃｍ²
サンブルサイズ：10ｍｍ×10ｍｍ×3ｍｍ
【００３７】
【表２】

【００３８】
上記の結果から、人工真皮用として発明したP(LA/CL)(50:50)の本願スポンジは優れた伸縮性を有するとともに、優れた圧縮弾性を有し、人工真皮用基材として優れた物性を有することが明らかになった。
【００３９】
【発明の効果】
生物由来の材料を使用しない合成生体吸収性高分子のみからなる真皮再生用基材を発明した。かかる真皮再生用基材は、当該用途に必要とされる柔軟性、分解吸収特性、安全性を有しており、製造の際にウイルスあるいはプリオン汚染に対する管理を必要としない。
【図面の簡単な説明】
【図１】実施例１で得られた真皮再生用基材の表面の走査電子顕微鏡像を示す写真である。
【図２】実施例１で得られた真皮再生用基材の断面の走査電子顕微鏡像を示す写真である。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a base material for dermis regeneration (artificial dermis), and more particularly, to a base material for dermis regeneration suitable for treating three skin defect wounds lost to the dermis layer in the field of dermatological plastic surgery.
[0002]
[Prior art]
A bilayer artificial skin was devised by Yanas et al. (J. Biomed. Mater. Res, 14, 65 (1980)) in which a silicone layer was bonded to a sponge composed of collagen and glycosaminoglycan. Later, Suzuki et al. Developed an artificial skin to which no glycosaminoglycan was added (Biomaterials, 11,356 (1990)), and its clinical effect was confirmed (Jpn.) Plast. Reconstr. After Surg. 36,479 (1993)), it is now widely used as a medical tool in the medical field, especially plastic surgery or dermatological surgery.
[0003]
When a sponge layer made of collagen is applied to a full-thickness skin defect wound, fibroblasts and capillaries invade and grow from the wound surface or edge, and the pores are filled with matrix collagen produced by fibroblasts, which is good in about 3 weeks Granulation tissue is regenerated. The silicone layer affixed to the upper surface serves to prevent external bacterial infection and control the transpiration of body fluids until regeneration is complete, and is peeled off after regeneration of the dermis is completed. After the dermis regeneration is completed, a thin epidermis is taken from other sites and transplanted onto the regenerated dermis layer. When the epidermis is transplanted directly into a full-thickness skin defect wound, the engraftment is poor, but since the dermis is regenerated, a good engraftment can be obtained even with a thin epidermis of about 5 thousandths of an inch.
[0004]
[Problems to be solved by the invention]
Currently, collagen derived from a living body is generally used as a matrix of a base material for artificial dermis. Collagen is extracted and purified from animals such as cows and pigs. Since the outbreak of mad cow disease (BSE) in recent years, it has become necessary to carefully manage contamination of viruses and prions for medical devices using materials derived from animals, particularly bovine. In particular, internal organs, spinal cords and the like cannot be used, and traceability is required for materials derived from low-risk sites. Collagen used in such artificial dermis is considered to be a site free of prion contamination such as skin or Achilles, but due to the nature of being used in living organisms, a thorough system is necessary for raw material management and 100% safety Sex is required.
[0005]
In view of such circumstances, an object of the present invention is to provide a base material for dermis regeneration (artificial dermis) using only a synthetic polymer as a raw material.
[0006]
[Means for Solving the Problems]
In recent years, various materials using synthetic polymers and bioabsorbable materials have been developed and widely used as scaffolds for regenerative medicine. If a base material for artificial dermis can be produced from these materials, it will not be necessary to manage virus or prion contamination.
[0007]
However, since artificial dermis is affixed to the skin, it can be used for living bodies with a flexible structure necessary for sufficient adhesion to the wound surface, a porous structure for allowing fibroblasts to invade and proliferate, and an appropriate period of degradation and absorption It was difficult to develop a synthetic material that satisfies the safety requirements.
[0008]
This time, the present inventors have invented a substrate for dermal regeneration made of a synthetic polymer having an appropriate period of degradation and absorption, flexibility and safety as a biomaterial.
[0009]
In addition, since it is considered that the exudate needs to penetrate well when it is applied to the wound surface, it was invented to make the material hydrophilic, and the effect was confirmed.
[0010]
In this respect, the present invention provides the following base material for dermal regeneration.
[0011]
Item 1. A base material for dermal regeneration comprising a porous body of a synthetic bioabsorbable polymer.
[0012]
Item 2. A dermal regeneration substrate having a two-layer structure of a porous layer made of a synthetic bioabsorbable polymer and a film made of a synthetic non-absorbable polymer.
[0013]
Item 3. Item 3. The dermal regeneration substrate according to Item 1 or 2, wherein the porous material is a sponge.
[0014]
Item 4. Item 3. The dermal regeneration substrate according to Item 1 or 2, wherein the bioabsorbable polymer is a copolymer of lactide and caprolactone.
[0015]
Item 5. Item 3. The dermal regeneration substrate according to Item 1 or 2, wherein the synthetic non-absorbable polymer is silicone.
[0016]
Item 6. Item 3. The dermal regeneration substrate according to Item 1 or 2, wherein the porous layer is subjected to a hydrophilic treatment.
[0017]
Item 7. Item 7. The dermal regeneration substrate according to Item 6, wherein the hydrophilization treatment is a plasma discharge treatment.
[0018]
DETAILED DESCRIPTION OF THE INVENTION
In the present invention, the synthetic bioabsorbable polymer is not particularly limited, but polyglycolic acid, polylactic acid (D-form, L-form, DL-form), polyε-caprolactone, poly (p-dioxanone) (PDS), poly ( β-hydroxybutyric acid) (PHB), absorbent polyamide, absorbent polycarbonate or copolymers thereof (for example, lactic acid-caprolactone copolymer, lactic acid-glycolic acid copolymer, glycolic acid-caprolactone copolymer, etc.) it can.
[0019]
In particular, a copolymer of lactide and caprolactone, particularly a copolymer of L-lactide and ε-caprolactone suitable for the application can be exemplified in terms of decomposition rate, flexibility, and the like.
[0020]
The molecular weight of the synthetic bioabsorbable polymer is about 2 to 1 million, preferably about 100 to 500,000.
[0021]
The thickness of the porous body layer is 1 to 10 mm, preferably 2 to 5 mm. The decomposition and absorption period is desirably about 3 weeks or more, particularly preferably about 5 weeks, during which the dermis layer is formed.
[0022]
The pore diameter of the porous layer is preferably 10 μm or more, preferably 100 to 300 μm, so that cells can enter. The method for producing this porous body layer is not particularly limited, but as an example, a porous material layer molded product having a desired form is obtained by placing a solution of a polymer material in a desired mold, freezing and then vacuum drying. Can be obtained. Or it is also possible to shape | mold by cutting the produced porous body into a suitable shape.
[0023]
Silicone can be used as the synthetic non-absorbable polymer.
[0024]
The thickness of the synthetic non-absorbable polymer film is about 50 to 500 μm, preferably about 100 to 300 μm. The film of a synthetic non-absorbable polymer can be adhered to the porous layer with or without using an adhesive.
[0025]
The hydrophilic treatment of the surface applied to the wound site of the porous layer includes plasma discharge treatment, corona discharge treatment, electron beam treatment, radiation treatment, ultraviolet treatment, and other physical treatments, and hydrophilic polymers such as polyethylene glycol. A chemical treatment using the above is mentioned, and a plasma discharge treatment is preferably exemplified.
[0026]
The elongation of the preferred dermal regeneration substrate of the present invention by a tensile fracture test is 200% or more, more preferably 500% or more.
[0027]
The compression recovery property according to the compression property test of the preferable dermis-regenerating substrate of the present invention is 50% or more, more preferably 80% or more.
[0028]
【Example】
Hereinafter, the present invention will be described with reference to examples.
[0029]
[Example 1]
A 5% dioxane solution of L-lactide-caprolactone copolymer (polymerization molar ratio 50:50; molecular weight 390,000) was prepared. This was poured into a Teflon (R) mold, frozen at −10 ° C. for 1 hour, and then freeze-dried at 30 ° C. for 24 hours. As a result, a swung sheet having a porous structure with a thickness of 3 mm was obtained.
[0030]
When this sponge was subjected to a tensile fracture test and a compression characteristic test using an autograph, it was confirmed to be a soft and strong sponge.
[0031]
Silicone (Shin-Etsu Chemical 1-component RTV rubber, deacetic acid type) was formed on a Teflon (R) sheet with a film forming machine (0.025 mm doctor blade), and the sponge was immediately applied. After the silicone was cured at about 60 ° C. for 3 hours and then peeled off from the Teflon (R) sheet, a substrate for regenerating the dermis of the present invention having a two-layer structure composed of a sponge and a silicone sheet was obtained. The surface (FIG. 1) and cross section (FIG. 2) of the scanning electron microscope image of this are shown in the photograph.
[0032]
[Example 2]
Sponge (thickness of about 3 mm, 5 cm × 5 cm) made of a hydrophilic treatment L-lactide-caprolactone copolymer (polymerization molar ratio 50:50; molecular weight 390,000) was subjected to plasma discharge treatment (device used: plasma reactor manufactured by Yamato Scientific) Model No .: PC101A) and processing conditions (output 300 watts, gas: air, gas pressure: 1 Torr, processing time: 3 minutes, 1.5 minutes, 30 seconds)).
[0033]
Distilled water (500 μl) was dropped into the prepared sample, and the time until the sample was completely infiltrated was measured.
[0034]
・ Non-treated area: not infiltrated after 24 hours ・ 30 seconds treatment: 3 hours ・ 1.5 minutes treatment: 1 hour ・ 3 minutes treatment: 20 minutes 3 weeks for regeneration of dermal tissue in full-thickness skin defect wounds Since it is necessary to the extent, it can be considered that the processing for 30 seconds is sufficient.
Test example 1
The following samples were subjected to a tensile fracture test and a compression property test.
(1) Sample polymer: L-lactide-caprolactone copolymer (polymerization molar ratio 50:50; molecular weight 390,000) 5% dioxane solution freezing temperature: −10 ° C.
Freeze drying: 30 ° C., 24 hours (2) Tensile rupture test The tensile rupture test was repeated 5 times under the following conditions, and the average value was calculated. The results are shown in Table 1.
Equipment used: Shimadzu Autograph AG-500B
Test speed: 50mm / min
Load cell: 5.0 kgf
Sample size: 10mm x 30mm x 3mm
Distance between chucks: 10mm
[0035]
[Table 1]

[0036]
(3) Compression characteristic test The compression characteristic test was repeated three times under the following conditions, and the average value was calculated. The results are shown in Table 2.
Equipment used: KES-FB3 (KATO TECH. Co. Ltd.)
Speed: 50mm / mim
Zone: 2cm ²
Sample size: 10mm x 10mm x 3mm
[0037]
[Table 2]

[0038]
From the above results, the present sponge of P (LA / CL) (50:50) invented for artificial dermis has excellent stretchability and excellent compression elasticity, and is excellent as a base material for artificial dermis. It became clear that it had physical properties.
[0039]
【The invention's effect】
Invented a base material for dermal regeneration consisting only of a synthetic bioabsorbable polymer that does not use biological materials. Such a dermal regeneration base material has the flexibility, decomposition and absorption characteristics, and safety required for the application, and does not require management of virus or prion contamination during production.
[Brief description of the drawings]
1 is a photograph showing a scanning electron microscope image of the surface of a substrate for dermis reproduction obtained in Example 1. FIG.
2 is a photograph showing a scanning electron microscope image of a cross section of the dermis-reproducing substrate obtained in Example 1. FIG.

Claims (6)

Ri Do from the porous body of synthetic bioabsorbable polymer,
The synthetic bioabsorbable polymer is a copolymer of lactide and caprolactone;
The average pore diameter of the porous body is 100 to 300 μm,
A base material for regenerating dermis having an elongation of 200% or more by a tensile fracture test and a compression recovery by a compression property test of 50% or more . A dermal regeneration substrate having a two-layer structure of a porous layer made of a synthetic bioabsorbable polymer and a film made of a synthetic non-absorbable polymer. The dermal regeneration substrate according to claim 1 or 2, wherein the porous body is made of sponge. The base material for dermal regeneration according to claim 2, wherein the synthetic non-absorbable polymer is silicone. The dermal regeneration base material according to claim 1 or 2, wherein the porous body layer has been subjected to a hydrophilic treatment. 6. The dermal regeneration substrate according to claim 5 , wherein the hydrophilization treatment is a plasma discharge treatment.

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